There is increasing evidence that obesity has its origins in early life. Predisposition is based on interactions between the genome and environmental influences acting through epigenetic modifications. Individuals most at risk are those whose ancestral line has made a rapid transition from a traditional to a Westernized style of life. The process involves not only metabolism, but also behavior. As a result, those people who are most at risk of obesity may be those least likely to respond to educational programs based on lifestyle modification. Understanding the mechanisms and pathways that underpin the early origins of obesity is vital if we are to make progress in addressing this major problem of modern life.